Biosensor systems usually provide an analysis of one or more analytes in biological fluids. The analysis typically includes a quantitative determination of the analyte in the biological fluid. The analysis is useful in the diagnosis and treatment of physiological abnormalities. For example, the determination of the glucose level in blood is important to diabetic individuals who frequently check their blood glucose level to regulate diet and/or medication. For other individuals, the monitoring of uric acid, lactate, cholesterol, bilirubin, and the like may be important.
Biosensor systems may be implemented using bench-top, portable, and other measuring devices. The portable devices may be hand-held and usually include a measuring device and a sensor strip. Typically, a sample of a biological fluid is introduced to the sensor strip, which is disposed in the measuring device for analysis. Biosensor systems may be designed to analyze one or more analytes and may use different volumes of biological fluids. Some biosensor systems may analyze a single drop of whole blood (WB), such as from 1-15 microliters (μL) in volume.
Biosensor systems usually measure an output signal to determine the analyte concentration in a sample of the biological fluid. The output signal is generated from an oxidation/reduction or redox reaction of the analyte. An enzyme or similar species may be added to the sample to enhance the redox reaction. The output signal may be an electric signal, light, or light converted to an electric signal. A biosensor system may generate the output signal using an optical sensor system or an electrochemical sensor system.
In optical systems, the analyte concentration is determined by measuring light that has interacted with a light-identifiable species, such as the analyte or a reaction or product formed from a chemical indicator reacting with the analyte redox reaction. An incident excitation beam from a light source is directed toward the sample. The light-identifiable species absorbs or shifts the wavelength of a portion of the incident beam, thus altering the wavelength or reducing the intensity of the incident beam. A detector collects and measures the attenuated or wavelength-altered incident beam, which is the output signal. In other optical systems, the chemical indicator fluoresces or emits light in response to the analyte redox reaction when illuminated by the excitation beam. A detector collects and measures the light, which is the output signal.
In electrochemical systems, the analyte concentration is determined by measuring an electrical signal, such as a current or potential. Typically, the analyte undergoes the redox reaction when an excitation signal is applied to the sample. The excitation signal usually is an electrical signal, such as a current or potential. The redox reaction generates an output signal in response to the excitation signal. The output signal usually is an electrical signal, such as a current or potential, which may be measured and correlated with the concentration of the analyte.
In electrochemical systems, the measuring device usually has electrical contacts that connect with electrical conductors in the sensor strip. The electrical connectors are connected by the conductors to electrodes that extend into the sample of the biological fluid. The measuring device applies the excitation signal through the electrical contacts to the electrical conductors, which convey the excitation signal into the sample through the electrodes. The redox reaction of the analyte generates an output signal in response to the excitation signal. The measuring device determines the analyte concentration in response to the output signal. Examples of portable measuring devices include the Ascensia Breeze® and Elite® meters of Bayer Corporation; the Precision® biosensors available from Abbott in Abbott Park, Ill.; Accucheck® biosensors available from Roche in Indianapolis, Ind.; and OneTouch Ultra® biosensors available from Lifescan in Milpitas, Calif. Examples of bench-top measuring devices include the BAS 100B Analyzer available from BAS Instruments in West Lafayette, Ind.; the CH Instruments' Electrochemical Workstation available from CH Instruments in Austin, Tex.; the Cypress Electrochemical Workstation available from Cypress Systems in Lawrence, Kans.; and the EG&G Electrochemical Instrument available from Princeton Research Instruments in Princeton, N.J.
Sensor strips may include reagents that react with the analyte in the sample of biological fluid. The reagents include an ionizing agent for facilitating the redox of the analyte, as well as any mediators or other substances that assist in transferring electrons between the analyte and the conductor. The ionizing agent may be an analyte specific enzyme, such as glucose oxidase or glucose dehydrogenase, to catalyze the oxidation of glucose in a WB sample. The reagents may include a binder that holds the enzyme and mediator together. In optical systems, the reagents include the chemical indicator along with another enzyme or like species to enhance the reaction of the chemical indicator with the analyte or products of the analyte redox reaction.
Most biosensor systems use correlation or calibration equations to determine the analyte concentration in a sample of a biological fluid. Correlation equations represent the relationship between output signals and analyte concentrations. From each correlation equation, an analyte concentration may be calculated for a particular output signal. The correlation equations are dependent on the temperature of the sample. The output signal for a particular analyte concentration may change due to the effect of temperature on the redox reaction of the analyte, enzyme kinetics, diffusion, and the like. A correlation equation may be needed for each possible sample temperature in order to calculate the analyte concentration from an output signal at a particular sample temperature.
To reduce the number of correlation equations used in the sample analysis, many biosensor systems attempt to provide analyte concentrations using one or more correlation equations for a particular reference temperature. The analyte concentration at a sample temperature usually is compensated for the difference between the sample temperature and the reference temperature to provide an analyte concentration at the reference temperature.
Some biosensor systems compensate for temperature by changing the output signal prior to calculating the analyte concentration from a correlation equation. The output signal usually is multiplied by a temperature correction coefficient or the like. The temperature-corrected output signal is used to determine the analyte concentration. Biosensor systems using a temperature-corrected output signal are described in U.S. Pat. Nos. 4,750,496 and 6,576,117.
Other biosensor systems compensate for temperature by changing the analyte concentration calculated by the correlation equation. The analyte concentration calculated from the correlation equation usually undergoes a temperature correction procedure to provide a temperature-corrected analyte concentration. Biosensor systems using a temperature-corrected analyte concentration are described in U.S. Pat. Nos. 5,366,609; 5,508,171; and 6,391,645.
Additional biosensor systems compensate for temperature by changing the output signal prior to calculating the analyte concentration from a correlation equation and/or by changing the analyte concentration calculated by the correlation equation. Biosensor systems using a temperature-corrected output signal and/or a temperature-corrected analyte concentration are described in U.S. Pat. Nos. 4,431,004 and 5,395,504.
While these temperature compensation methods balance various advantages and disadvantages, none are ideal. These methods may not fully incorporate various effects of different sample temperatures on the redox reaction of the analyte, the enzyme and mediator kinetics, and diffusion. These methods may not adequately address effects of different analyte concentrations on enzyme kinetics and diffusion at different sample temperatures. These methods also may not adequately address effects of different analyte concentrations on the redox reaction at different sample temperatures. In addition, the changes to the output signal and/or the calculated analyte concentration may introduce or magnify errors related to the determination of the analyte concentration from the output signal.
Accordingly, there is an ongoing need for improved biosensor systems, especially those that may provide increasingly accurate and precise analyte concentrations at a reference temperature. The systems, devices, and methods of the present invention overcome at least one of the disadvantages associated with conventional biosensor systems.